Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial

被引:3425
作者
Mitsudomi, Tetsuya [1 ]
Morita, Satoshi [2 ]
Yatabe, Yasushi [3 ]
Negoro, Shunichi [4 ]
Okamoto, Isamu [6 ]
Tsurutani, Junji [6 ]
Seto, Takashi [7 ]
Satouchi, Miyako [5 ]
Tada, Hirohito [8 ]
Hirashima, Tomonori [9 ]
Asami, Kazuhiro [10 ]
Katakami, Nobuyuki [11 ]
Takada, Minoru [12 ]
Yoshioka, Hiroshige [13 ]
Shibata, Kazuhiko [14 ]
Kudoh, Shinzoh [15 ]
Shimizu, Eiji [16 ]
Saito, Hiroshi [17 ]
Toyooka, Shinichi [18 ]
Nakagawa, Kazuhiko [6 ]
Fukuoka, Masahiro [12 ]
机构
[1] Aichi Canc Ctr Hosp, Dept Thorac Surg, Chikusa Ku, Nagoya, Aichi 4648681, Japan
[2] Yokohama City Univ, Med Ctr, Dept Biostat & Epidemiol, Yokohama, Kanagawa 232, Japan
[3] Aichi Canc Ctr Hosp, Dept Pathol & Mol Genet, Nagoya, Aichi 4648681, Japan
[4] Hyogo Canc Ctr, Dept Med Oncol, Akashi, Hyogo, Japan
[5] Hyogo Canc Ctr, Dept Thorac Oncol, Akashi, Hyogo, Japan
[6] Kinki Univ, Sch Med, Dept Med Oncol, Osaka 589, Japan
[7] Kyushu Natl Canc Ctr, Dept Thorac Oncol, Fukuoka, Japan
[8] Osaka City Gen Hosp, Dept Gen Thorac Surg, Osaka, Japan
[9] Osaka Prefectural Med Ctr Resp & Allerg Dis, Dept Thorac Oncol, Habikino, Japan
[10] Natl Hosp Org Kinki Chuo Chest Med Ctr, Dept Resp Med, Sakai, Osaka, Japan
[11] Med Kobe City Med Ctr Gen Hosp, Div Pulm, Clin Res Ctr, Kobe, Hyogo, Japan
[12] Kinki Univ, Sch Med, Sakai Hosp, Dept Med Oncol, Sakai, Osaka, Japan
[13] Kurashiki Cent Hosp, Dept Resp Med, Kurashiki, Okayama, Japan
[14] Koseiren Takaoka Hosp, Dept Med Oncol, Takaoka, Toyama, Japan
[15] Osaka City Univ, Grad Sch Med, Dept Resp Med, Osaka 558, Japan
[16] Tottori Univ, Fac Med, Div Med Oncol & Mol Respirol, Tottori 680, Japan
[17] Aichi Hosp, Aichi Canc Ctr, Dept Resp Med, Okazaki, Aichi, Japan
[18] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg, Okayama 7008530, Japan
关键词
PREVIOUSLY TREATED PATIENTS; JAPANESE PATIENTS; II TRIAL; SURVIVAL; GENE; CHEMOTHERAPY; MULTICENTER; EFFICACY; DISEASE; ASSAY;
D O I
10.1016/S1470-2045(09)70364-X
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Patients with non-small-cell lung cancer harbouring mutations in the epidermal growth factor receptor (EGFR) gene respond well to the EGFR-specific tyrosine kinase inhibitor gefitinib. However, whether gefitinib is better than standard platinum doublet chemotherapy in patients selected by EGFR mutation is uncertain. Methods We did an open label, phase 3 study (WJTOG3405) with recruitment between March 31, 2006, and June 22, 2009, at 36 centres in Japan. 177 chemotherapy-naive patients aged 75 years or younger and diagnosed with stage IIIB/IV non-small-cell lung cancer or postoperative recurrence harbouring EGFR mutations (either the exon 19 deletion or L858R point mutation) were randomly assigned, using a minimisation technique, to receive either gefitinib (250 mg/day orally; n=88) or cisplatin (80 mg/m(2), intravenously) plus docetaxel (60 mg/m(2), intravenously; n=89), administered every 21 days for three to six cycles. The primary endpoint was progression-free survival. Survival analysis was done with the modified intention-to-treat population. This study is registered with UMIN (University Hospital Medical Information Network in Japan), number 000000539. Findings Five patients were excluded (two patients were found to have thyroid and colon cancer after randomisation, one patient had an exon 18 mutation, one patient had insufficient consent, and one patient showed acute allergic reaction to docetaxel). Thus, 172 patients (86 in each group) were included in the survival analyses. The gefitinib group had significantly longer progression-free survival compared with the cisplatin plus docetaxel goup, with a median progression-free survival compared with the cisplatin plus docetaxel goup, with a median progression-free survival time of 9.2 months (95% CI 8.0-13.9) versus 6.3 months (5.8-7.8; HR 0.489, 95% CI 0.336-0.710, log-rank p<0.0001). Myelosuppression, alopecia, and fatigue were more frequent in the cisplatin plus docetaxel group, but skin toxicity, liver dysfunction, and diarrhoea were more frequent in the gefitinib group. Two patients in the gefitinib group developed interstitial lung disease (incidence 2.3%), one of whom died. Interpretation Patients with lung cancer who are selected by EGFR mutations have longer progression-free survival if they are treated with gefitinib than if they are treated with cisplatin plus docetaxel.
引用
收藏
页码:121 / 128
页数:8
相关论文
共 33 条
[1]   Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib [J].
Ando, M ;
Okamoto, I ;
Yamamoto, N ;
Takeda, K ;
Tamura, K ;
Seto, T ;
Ariyoshi, Y ;
Fukuoka, M .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (16) :2549-2556
[2]  
[Anonymous], 1999, STAT MED, V18, P1905
[3]  
[Anonymous], J THORAC ONCOL S
[4]  
Cappuzzo F, 2009, J THORAC ONCOL S, V4
[5]   Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib [J].
Eberhard, DA ;
Johnson, BE ;
Amler, LC ;
Goddard, AD ;
Heldens, SL ;
Herbst, RS ;
Ince, WL ;
Jänne, PA ;
Januario, T ;
Johnson, DH ;
Klein, P ;
Miller, VA ;
Ostland, MA ;
Ramies, DA ;
Sebisanovic, D ;
Stinson, JA ;
Zhang, YR ;
Seshagiri, S ;
Hillan, KJ .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (25) :5900-5909
[6]   Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer [J].
Fukuoka, M ;
Yano, S ;
Giaccone, G ;
Tamura, T ;
Nakagawa, K ;
Douillard, JY ;
Nishiwaki, Y ;
Vansteenkiste, J ;
Kudoh, S ;
Rischin, D ;
Eek, R ;
Horai, T ;
Noda, K ;
Takata, I ;
Smit, E ;
Averbuch, S ;
Macleod, A ;
Feyereislova, A ;
Dong, RP ;
Baselga, J .
JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (12) :2237-2246
[7]   Molecular origins of cancer: Lung cancer [J].
Herbst, Roy S. ;
Heymach, John V. ;
Lippman, Scott M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (13) :1367-1380
[8]   Impact of Epidermal Growth Factor Receptor and KRAS Mutations on Clinical Outcomes in Previously Untreated Non-Small Cell Lung Cancer Patients: Results of an Online Tumor Registry of Clinical Trials [J].
Jackman, David M. ;
Miller, Vincent A. ;
Cioffredi, Leigh-Anne ;
Yeap, Beow Y. ;
Jaenne, Pasi A. ;
Riely, Gregory J. ;
Ruiz, Marielle Gallegos ;
Giaccone, Giuseppe ;
Sequist, Lecia V. ;
Johnson, Bruce E. .
CLINICAL CANCER RESEARCH, 2009, 15 (16) :5267-5273
[9]  
Jemal A, 2009, CA-CANCER J CLIN, V59, P225, DOI [10.3322/caac.20006, 10.3322/caac.21387]
[10]   Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial [J].
Kim, Edward S. ;
Hirsh, Vera ;
Mok, Tony ;
Socinski, Mark A. ;
Gervais, Radj ;
Wu, Yi-Long ;
Li, Long-Yun ;
Watkins, Claire L. ;
Sellers, Mark V. ;
Lowe, Elizabeth S. ;
Sun, Yan ;
Liao, Mei-Lin ;
Osterlind, Kell ;
Reck, Martin ;
Armour, Alison A. ;
Shepherd, Frances A. ;
Lippman, Scott M. ;
Douillard, Jean-Yves .
LANCET, 2008, 372 (9652) :1809-1818